Fragment crystallizable region of human Immunoglobulin G (IgG-Fc)

The Fragment crystallizable (Fc) region of human Immunoglobulin G (IgG) is the C-terminal portion of the antibody molecule, consisting of two identical heavy chain constant domains (CH2 and CH3) [1.2.2, 1.2.3]. It serves as the critical link between the specificity of the adaptive immune system and the effector functions of the innate immune system by binding to Fc gamma receptors (FcγRs) on leukocytes and the C1q component of the complement system [1.2.1, 1.5.2]. These interactions trigger essential immune responses, including antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC) [1.2.4, 1.4.1]. Additionally, the Fc region interacts with the neonatal Fc receptor (FcRn), which protects IgG from lysosomal degradation and regulates its long serum half-life and placental transfer [1.3.2, 1.5.2]. In autoimmune diseases, the Fc region of pathogenic autoantibodies is responsible for mediating tissue damage and inflammation [1.3.1, 1.5.3]. Consequently, the Fc region is a major focus of therapeutic intervention, either through enzymatic cleavage by drugs like Imlifidase to neutralize autoantibodies or through the use of FcRn inhibitors to accelerate their clearance [1.1.2, 1.5.3]. Furthermore, the Fc region is widely utilized as a structural scaffold in drug development to create Fc-fusion proteins and engineered antibodies with optimized pharmacokinetic and pharmacodynamic properties [1.5.1, 1.5.2].

Other names

Fc regionFc fragmentIgG constant regionFragment crystallizable

The Fc region of IgG mediates immune effector functions by binding to Fc gamma receptors (FcγRs) and the C1q component of the complement system, leading to processes such as ADCC, ADCP, and CDC [1.2.1, 1.5.2]. It also interacts with the neonatal Fc receptor (FcRn) to regulate IgG serum half-life through a pH-dependent recycling mechanism [1.3.2, 1.5.2]. Therapeutic strategies targeting this region include enzymatic cleavage by Imlifidase to neutralize pathogenic IgG [1.5.3] and the use of FcRn inhibitors (e.g., Efgartigimod, Rozanolixizumab) to block the Fc-binding site on FcRn, thereby accelerating the clearance of autoantibodies [1.1.2, 1.5.3].